Intervention

152 patients were allocated to prone positioning and were continuously kept prone for ≥ 6 hours each day for 10 days. Patients
were assessed in the supine position each morning. A change to the prone position was triggered by a PaO2:FiO2 ratio ≤ 200 with a PEEP ≥ 5 cm water, or a PaO2:FiO2 ratio ≤ 300 with a PEEP ≥ 10 cm water. 152 patients were allocated to conventional (supine) positioning.

Main outcome measures

Main outcomes were death at 10 days (end of intervention), during ICU stay, and at 6 months. Other outcomes included improvement
in respiratory failure and organ dysfunction; presence, site, and severity of pressure sores; and accidental displacement
of tracheal or thoracotomy tubes or loss of venous access.

Main results

Analysis was by intention to treat. The prone and supine groups had similar 10 day mortality, ICU mortality, and 6 month mortality
(table), incidence of organ dysfunction, percentage of patients with new or worsening pressure sores, number of days with
pressure sores, accidental displacement of tubes, and loss of venous access. Patients in the prone group had slightly greater
increases in the PaO2:FiO2 ratio on morning assessments (average change 63.0 v 44.6, p=0.02) and more new or worsening pressure sores (2.7 v 1.9 per patient, p=0.004).

Commentary

The trial by Gattinoni et al is an important part of an international effort to determine the effect of prone ventilation on survival in patients with
acute lung injury. Prone positioning makes good sense physiologically; preclinical and clinical investigations have provided
mechanistic information and observational studies, including >260 patients with severe acute lung injury, suggest that 60%–70%
of patients have an immediate improvement in oxygenation. However, intensive care clinicians are increasingly faced with the
frustrating reality that physiological improvement does not always lead to a survival benefit. More importantly, the potential
for such serious complications of prone ventilation as inadvertent extubation, loss of venous access and chest tubes, delayed
cardiopulmonary resuscitation, and blindness, is clear. As a result, the intensive care world has awaited the completion of
this study with great anticipation.

The results, disappointingly, fail to show a survival benefit in patients cared for in the prone position for ≥ 6 consecutive
hours each day. However, the true effect of prone ventilation remains unclear. Examination of the confidence intervals reveals
that prone positioning for ≥ 6 consecutive hours each day may reduce ICU mortality by as much as 16% (in which case, we would
use it routinely) or may increase ICU mortality by as much as 32% (in which case, we would not); therefore, more randomised
trials are necessary to clarify the role of prone positioning in patients with acute lung injury. In addition, many clinicians
believe that 6 hours per day is insufficient to achieve the full potential of prone ventilation. Two randomised trials of
prone ventilation are currently underway in Europe, with protocols for longer daily periods of prone ventilation. For now,
as the best available evidence suggests no survival benefit and a potential for serious complications, prone positioning should
be reserved for patients who are profoundly hypoxemic (as indicated by an intriguing post hoc analysis of these data) or for
those enrolled in further clinical research.